In the past few years there have been significant advances which have changed the face of chronic urticaria. In this review, we aim to update physicians about clinically relevant advances in the classification, diagnosis and management of chronic urticaria that have occurred in recent years. These include clarification of the terminology used to describe and classify urticaria. We also detail the development and validation of instruments to assess urticaria and understand the impairment on quality-of-life and the morbidity caused by this disease. Additionally, the approach to management of chronic urticaria now focuses on evidence-based use of non-impairing, non-sedating H1-antihistamines given initially in standard doses and if this is not effective, in up to 4-fold doses. For urticaria refractory to H1-antihistamines, omalizumab treatment has emerged as an effective, safe option.
Chronic urticaria; Diagnosis; Classification; Management; Immunology; Antihistamines; Up-dosing; Omalizumab
Eosinophil degranulation of peroxidase promotes DC activation and mobilization from the intestine to LNs to induce Th2 immunity and food allergy.
Eosinophils natively inhabit the small intestine, but a functional role for them there has remained elusive. Here, we show that eosinophil-deficient mice were protected from induction of Th2-mediated peanut food allergy and anaphylaxis, and Th2 priming was restored by reconstitution with il4+/+ or il4−/− eosinophils. Eosinophils controlled CD103+ dendritic cell (DC) activation and migration from the intestine to draining lymph nodes, events necessary for Th2 priming. Eosinophil activation in vitro and in vivo led to degranulation of eosinophil peroxidase, a granule protein whose enzymatic activity promoted DC activation in mice and humans in vitro, and intestinal and extraintestinal mouse DC activation and mobilization to lymph nodes in vivo. Further, eosinophil peroxidase enhanced responses to ovalbumin seen after immunization. Thus, eosinophils can be critical contributors to the intestinal immune system, and granule-mediated shaping of DC responses can promote both intestinal and extraintestinal adaptive immunity.
Prevalence of allergic diseases in infants, whose parents and siblings do not have allergy, is approximately 10% and reaches 20–30% in those with an allergic first-degree relative. Intestinal microbiota may modulate immunologic and inflammatory systemic responses and, thus, influence development of sensitization and allergy. Probiotics have been reported to modulate immune responses and their supplementation has been proposed as a preventive intervention.
The World Allergy Organization (WAO) convened a guideline panel to develop evidence-based recommendations about the use of probiotics in the prevention of allergy.
We identified the most relevant clinical questions and performed a systematic review of randomized controlled trials of probiotics for the prevention of allergy. We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to develop recommendations. We searched for and reviewed the evidence about health effects, patient values and preferences, and resource use (up to November 2014). We followed the GRADE evidence-to-decision framework to develop recommendations.
Currently available evidence does not indicate that probiotic supplementation reduces the risk of developing allergy in children. However, considering all critical outcomes in this context, the WAO guideline panel determined that there is a likely net benefit from using probiotics resulting primarily from prevention of eczema. The WAO guideline panel suggests: a) using probiotics in pregnant women at high risk for having an allergic child; b) using probiotics in women who breastfeed infants at high risk of developing allergy; and c) using probiotics in infants at high risk of developing allergy. All recommendations are conditional and supported by very low quality evidence.
WAO recommendations about probiotic supplementation for prevention of allergy are intended to support parents, clinicians and other health care professionals in their decisions whether to use probiotics in pregnancy and during breastfeeding, and whether to give them to infants.
Electronic supplementary material
The online version of this article (doi:10.1186/s40413-015-0055-2) contains supplementary material, which is available to authorized users.
Allergy; Prevention; Probiotics; Practice guidelines; GRADE
The effect of sublingual Timothy grass immunotherapy tablet 2800 BAU (grass SLIT-T) has been evaluated in three North American trials in adults and children who have allergic rhinitis with or without conjunctivitis (AR/C). This paper examines the effects of grass SLIT-T in Canadians.
Data for grass-allergic Canadians in three randomized, placebo-controlled, double-blind trials were analyzed post hoc: 1) adults ≥18 y, grass-pollen season [GPS] 2009; 2) children 5– <18 y, 2009; and 3) adults 18–65 y and children 5– <18 y, GPS 2012. Data from the GPS 2009 trials were pooled to provide a more precise estimate of treatment effects than the individual studies would provide. In every trial, participants received once-daily grass SLIT-T or placebo approximately 12 weeks before and continuing throughout the GPS. Participants used daily electronic diaries to record AR/C symptoms and medication use for treatment of symptoms. The therapeutic effect of grass SLIT-T was measured as a total combined score (TCS = daily symptom score + daily medication score) averaged over the entire GPS. Safety was assessed by monitoring adverse events (AEs).
In the three trials, 386 Canadian participants were randomized; the overall population had 2284 participants. Canadian participants treated with grass SLIT-T in the pooled adult-pediatric 2009 trials showed a 38% mean TCS reduction relative to placebo (-2.06 difference [95% CI: -3.72, -0.39]; 3.32 vs. 5.37). Participants treated with grass SLIT-T in the adult-pediatric 2012 trial showed a 37% median TCS reduction relative to placebo (-1.53 difference [95% CI: -2.1, -0.3]; 2.58 vs. 4.11). Similar efficacy findings were observed over the peak GPS. Approximately 90% of treatment-related AEs were mild or moderate in severity. Two Canadian participants had moderate systemic allergic reactions (skin, respiratory, abdominal symptoms) to grass SLIT-T; symptoms resolved within 1 hour without medical intervention or treatment. No serious or life-threatening treatment-related AEs occurred.
The 2800 BAU Timothy grass SLIT-T significantly improved AR/C induced by Timothy grass pollen in adults and children ≥5 y in Canadians, which was consistent with the robust efficacy observed in the overall trial population. The treatment was generally well tolerated.
Clinicaltrials.gov identifiers NCT00562159, NCT00550550, NCT01385371.
Allergic rhinitis; Conjunctivitis; Timothy grass pollen; Sublingual immunotherapy tablet
Hereditary angioedema (HAE) is a disease which is associated with random and often unpredictable attacks of painful swelling typically affecting the extremities, bowel mucosa, genitals, face and upper airway. Attacks are associated with significant functional impairment, decreased Health Related Quality of Life, and mortality in the case of laryngeal attacks. Caring for patients with HAE can be challenging due to the complexity of this disease. The care of patients with HAE in Canada is neither optimal nor uniform across the country. It lags behind other countries where there are more organized models for HAE management, and where additional therapeutic options are licensed and available for use. The objective of this guideline is to provide graded recommendations for the management of patients in Canada with HAE. This includes the treatment of attacks, short-term prophylaxis, long-term prophylaxis, and recommendations for self-administration, individualized therapy, quality of life, and comprehensive care. It is anticipated that by providing this guideline to caregivers, policy makers, patients and their advocates, that there will be an improved understanding of the current recommendations regarding management of HAE and the factors that need to be considered when choosing therapies and treatment plans for individual patients. The primary target users of this guideline are healthcare providers who are managing patients with HAE. Other healthcare providers who may use this guideline are emergency physicians, gastroenterologists, dentists and otolaryngologists, who will encounter patients with HAE and need to be aware of this condition. Hospital administrators, insurers and policy makers may also find this guideline helpful.
Electronic supplementary material
The online version of this article (doi:10.1186/1710-1492-10-50) contains supplementary material, which is available to authorized users.
Hereditary angioedema; Guideline; Recommendations; Acute attacks; Short-term prophylaxis; Long-term prophylaxis; Self-administration; Individualized therapy; Quality of life; Comprehensive care; GRADE
Examining deaths caused by anaphylaxis may help identify factors that may decrease the risk of these unfortunate events. However, information on fatal anaphylaxis is limited. The objectives of our study were to examine all cases of fatal anaphylaxis in Ontario to determine cause of death, associated features, co factors and trends in mortality. The identification of these factors is important for developing effective strategies to overcome gaps in monitoring and treatment of patients with food allergies and risk for anaphylaxis.
This was a retrospective case-series analysis of all causes of anaphylaxis-related deaths using data from the Ontario Coroner’s database between 1986 and 2011. Quantitative data (e.g. demographic) were analyzed using descriptive statistics and frequency analysis using SPSS. Qualitative data were analyzed using content analysis of grounded theory methodology.
We found 92 deaths in the last 26 years related to anaphylaxis. Causes of death, in order of decreasing frequency, included food (40 cases), insect venom (30 cases), iatrogenic (16 cases), and idiopathic (6 cases). Overall, there appears to be a decline in the frequency of food related deaths, but an increase in iatrogenic causes of fatalities. We found factors associated with fatal anaphylaxis included: delayed epinephrine administration, asthma, allergy to peanut, food ingestion outside the home, and teenagers with food allergies.
Our findings indicate the need to improve epinephrine auto-injector use in acute reactions, particularly for teens and asthmatics with food allergies. In addition, education can be improved among food service workers and food industry in order to help food allergic patients avoid potentially fatal allergens. The increasing trend in iatrogenic related anaphylaxis is concerning, and requires monitoring and more investigation.
Anaphylaxis; Severe allergic reaction; Anaphylaxis mortality; Food allergy; Medication allergy; Adverse drug reaction; Venom allergy; Insect sting allergy; Iatrogenic anaphylaxis
Insufficient knowledge of food allergy and anaphylaxis has been identified by caregivers as an important barrier to coping, and a potential cause of fear and anxiety, particularly for those with children newly diagnosed with food allergy.
The purpose of the study was to better understand the experiences of caregivers of children with a first allergic reaction to food, and to identify any deficiencies in the information received at diagnosis.
A mixed-methods study consisting of an online survey administered to the Anaphylaxis Canada online registry (a patient support group database of approximately 10,000 members), and a follow-up qualitative interview with a subset of survey participants. Analysis consisted of frequency analysis (quantitative and qualitative data) and descriptive statistics to calculate proportions and means with standard deviations. Qualitative analyses were guided by the constant comparative method of grounded theory methodology.
Of 293 survey respondents, 208 were eligible to complete the survey (first allergic reaction to food within 12 months of the study), and 184 respondents consented. Identified gaps included education about food allergy, anaphylaxis management, for example, how to use epinephrine auto- injectors, and coping strategies for fear and anxiety. The qualitative follow-up study supported these findings, yielding 3 major themes: 1) lack of provision of information following the episode on the recognition and management of food allergy related allergic reactions, 2) prolonged wait times for an allergist, and 3) significant family anxiety.
The online survey highlighted multiple deficiencies at diagnosis, findings which were supported by the follow up qualitative study. Results will inform the development of educational strategies for patients newly diagnosed with food allergy.
Anaphylaxis; Food allergy; Qualitative methods
School personnel in contact with students with life-threatening allergies often lack necessary supports, creating a potentially dangerous situation. Sabrina’s Law, the first legislation in the world designed to protect such children, requires all Ontario public schools to have a plan to protect children at risk. Though it has captured international attention, the differences a legislative approach makes have not been identified. Our study compared the approaches to anaphylaxis prevention and management in schools with and without legislation.
Legislated (Ontario) and non-legislated (Alberta, British Columbia, Newfoundland and Labrador, and Quebec) environments were compared. School board anaphylaxis policies were assessed for consistency with Canadian anaphylaxis guidelines. Parents of at-risk children and school personnel were surveyed to determine their perspectives on school practices. School personnel’s EpiPen technique was assessed.
Consistency of school board policies with anaphylaxis guidelines was significantly better in a legislated environment (p=0.009). Parents in a legislated environment reported more comprehensive anaphylaxis emergency forms (p< 0.001), while school personnel in non-legislated environments reported more comprehensive forms (p=0.004). Despite school personnel in both environments receiving EpiPen training (>80%), suboptimal technique was commonly observed. However, school personnel in the legislated environment had better technique (p < 0.001).
Our results suggest that school boards in legislated environments have made greater efforts to support students at-risk for anaphylaxis compared to non-legislated environments. However, significant gaps exist in both environments, especially with respect to EpiPen administration, content and distribution of anaphylaxis emergency forms, and awareness of school procedures by school personnel and parents.
Anaphylaxis; life-threatening allergies; policy; Sabrina’s Law; school
The immunological and clinical parameters that are associated with asthma remission are poorly understood. The cytokine and local mediator changes associated with the resolution of asthma symptoms were examined in three groups of subjects 12–18 years of age (n = 15 in each group): (a) continuing asthma group (CA) who had persistent symptoms since early childhood, (b) an age, sex and atopic status-matched group who had persistent symptoms in early childhood but in whom these had resolved (RA), and (c) a non-atopic, non-asthmatic control group. Clinical parameters, sputum cell counts, peripheral blood mononuclear cell (PBMC) cytokine production and activation marker expression were determined. All of the CA had methacholine airway hyperresponsiveness compared with only half of the RA subjects. The CA showed elevated numbers of eosinophils and increased ECP and IL-5 in sputum, which were not observed in the RA. PBMC cytokine studies revealed increased production of the type 1 cytokines IL-12, IFN-γ and TNF-α in the CA group compared with the RA group, under a range of activation conditions, however, the production of IL-4 and IL-5 were unchanged. These findings suggest that decreased type 1 cytokine expression as well as decreased eosinophilic inflammation is associated with the resolution of asthma symptoms.
Asthma in children; Eosinophils; IL-5; TNF-α; IL-12
There has been no large study characterizing selection bias in allergy and evaluating school personnel’s ability to use an epinephrine auto-injector (EpiPen®). Our objective was to determine if the consent process introduces selection bias by comparing 2 methods of soliciting participation of school personnel in a study evaluating their ability to demonstrate the EpiPen®.
School personnel from randomly selected schools in Quebec were approached using a 1) partial or 2) full disclosure approach and were assessed on their ability to use the EpiPen® and identify anaphylaxis.
343 school personnel participated. In the full disclosure group, the participation rate was lower: 21.9% (95%CI, 19.0%-25.2%) versus 40.7% (95%CI, 36.1%-45.3%), but more participants achieved a perfect score: 26.3% (95%CI, 19.6%-33.9%) versus 15.8% (95%CI, 10.8%-21.8%), and identified 3 signs of anaphylaxis: 71.8% (95%CI, 64.0%-78.7%) versus 55.6% (95%CI, 48.2%-62.9%).
Selection bias is suspected as school personnel who were fully informed of the purpose of the assessment were less likely to participate; those who participated among the fully informed were more likely to earn perfect scores and identify anaphylaxis. As the process of consent can influence participation and bias outcomes, researchers and Ethics Boards need to consider conditions under which studies can proceed without full consent. Despite training, school personnel perform poorly when asked to demonstrate the EpiPen®.
Anaphylaxis; Epinephrine; Food allergy; School; Treatment; Selection bias; Consent bias; Volunteer bias
Allergic rhinitis (AR) is a common problem and we sought to examine the burden of disease and its management in Canada from the perspectives of patients and physicians.
Two parallel, Canadawide structured telephone interviews surveyed 1,001 AR patients and 160 physicians in July 2006.
44% of patients had experienced nasal symptoms unrelated to a cold and 20% had a physician diagnosis of AR. At screening 27% reported asthma, 15% chronic or recurrent sinusitis and 5% nasal polyps. With attacks nasal congestion and runny nose were the most bothersome symptoms. Other problems experienced were fatigue (46%), poor concentration (32%), and reduced productivity (23%). Most (77%) had not seen a physician in the past year. Physicians estimated they prescribed intranasal cortico steroids (INCS) to most AR patients (77%) consistent with guidelines but only 19% of patients had used one in the last month. Only 48% of patients were very satisfied with their current INCS. 41% of AR patients reported discontinuing their INCS with the most common reason being a perceived lack of long-lasting symptom relief (44%). 52% of patients felt that their current INCS lost effectiveness over 24 h. The most common INCS side effects included dripping down the throat, bad taste, and dryness. Most AR patients reported lifestyle limitations despite treatment (66%). 61% of patients felt that their symptoms were only somewhat controlled or poorly/not controlled during their worst month in the past year.
AR symptoms are common and many patients experience inadequate control. Physicians report they commonly prescribe intranasal corticosteroids, but patient’s perceived loss of efficacy and side effects lead to their discontinuation. Persistent relief of allergic rhinitis symptoms remains a major unmet need. Better treatments and education are required.
Rhinitis, Allergic; Anti-allergic agents; Administration, Intranasal; Quality of life
Allergen immunotherapy (IT) is a key component of allergy practice, however fellows state that there is inadequate IT exposure during their training. In response, the Canadian Society of Allergy and Clinical Immunology (CSACI) unveiled the first ever IT Training Manual for fellows-in-training at the annual 2010 CSACI meeting. The manual was distributed during a faculty-led teaching session. This was a pilot investigation to determine the perspectives of fellows in training about the IT training manual.
Canadian fellows-in-training in Allergy and Clinical Immunology (list derived from CSACI) were contacted via email to complete a survey (using survey monkey), both quantitative (Likert scales) and qualitative, to assess their opinion on the faculty-led session on IT and the IT Training Manual.
Sixty-nine Canadian fellows-in-training were invited to complete the survey and 16 (23%). Fifty-four percent of 13 respondents were in their first year of fellowship. Seven respondents (58% of 12 respondents) attended the 2010 CSACI fellow-in-training session and received the IT Training Manual. One respondent commented that it was “more information than we've had in all of our fellowship!” The same 7 respondents “somewhat liked” or “liked” the large group format, but felt that the experience could be improved in the future with the addition of cased-based learning in smaller groups. One respondent commented that “as in intro, it was good in a larger setting.” All 7 respondents felt that their understanding of IT was positively impacted by the faculty-led session. Eighty-six percent of 7 respondents indicated that the Training Manual “somewhat impacted” to “very much impacted” their understanding of IT. One commenter stated that “it is the basis of my knowledge thus far.” Most respondents (86%) preferred the current paper booklet format of the IT Training Manual.
The results of this pilot survey demonstrate that some fellows-in-training found the faculty-led session on IT and the IT Training Manual useful. Future studies will help to further elucidate the utility of these 2 educational interventions.
Allergen immunotherapy (IT) is a key component of allergy practice of allergy. Canadian fellows-in-training have expressed concern that they receive inadequate exposure to IT in their training programs.
Canadian fellows-in-training in Allergy and Clinical Immunology, identified through the Canadian Society of Allergy and Clinical Immunology (CSACI), were contacted via email to complete a pilot survey (using survey monkey) to assess their exposure to, experience with, and comfort level in using IT.
Sixty-nine Canadian fellows-in-training were invited to complete the survey and 16 (23%) completed at least part of the survey. Fifty-four percent of 13 respondents were in their first year of fellowship. Fifty percent of 12 respondents were internal medicine trained. Eighty-three percent of 12 respondents acknowledged exposure to IT during their training. Eighty percent of 10 respondents had previously written a prescription for IT; 71% and 43% of 7 respondents had written 1 to 5 prescriptions for aeroallergen and stinging venom IT, respectively. Only 50% of 12 respondents felt comfortable prescribing IT. The most common reason cited was lack of experience; however, one respondent wrote that he/she would feel uncomfortable prescribing IT without using the standardized hospital IT form. Sixty-seven percent of 12 respondents had previously administered IT to a patient. Sixteen percent of 12 respondents felt uncomfortable administering IT due to lack of experience. Fifty percent of 12 respondents had treated a patient having an allergic reaction to IT and 100% of these same respondents felt "somewhat comfortable" to "very comfortable" in responding to an allergic reaction to IT. Seventy-five percent of 12 respondents agreed that a formal clinical rotation in IT would be helpful.
The results of this pilot survey demonstrate that Canadian fellows-in-training in Allergy and Clinical Immunology are not receiving adequate exposure and training in IT. Future studies will help to explore this subject in more detail.
Food allergy is defined as an adverse immunologic response to a dietary protein. Food-related reactions are associated with a broad array of signs and symptoms that may involve many bodily systems including the skin, gastrointestinal and respiratory tracts, and cardiovascular system. Food allergy is a leading cause of anaphylaxis and, therefore, referral to an allergist for appropriate and timely diagnosis and treatment is imperative. Diagnosis involves a careful history and diagnostic tests, such as skin prick testing, serum-specific immunoglobulin E (IgE) testing and, if indicated, oral food challenges. Once the diagnosis of food allergy is confirmed, strict elimination of the offending food allergen from the diet is generally necessary. For patients with significant systemic symptoms, the treatment of choice is epinephrine administered by intramuscular injection into the lateral thigh. Although most children “outgrow” allergies to milk, egg, soy and wheat, allergies to peanut, tree nuts, fish and shellfish are often lifelong. This article provides an overview of the epidemiology, pathophysiology, diagnosis, management and prognosis of patients with food allergy.
Research has shown that the long term management of food allergy is suboptimal. Our study aims to provide direction for improvement, by evaluating food allergy management from the perspective of, food allergic patients or their caregivers, and allergists in selected outpatient settings in Ontario.
This two-part study included an anonymous questionnaire completed by patients or their caregivers in allergy clinics, and a qualitative interview with allergists. In Part A, food allergic patients or their caregivers were surveyed about information they received on food allergy, their level of confidence with self-management, and their learning needs. In Part B, allergists were interviewed about teaching priorities and the challenges and strategies that currently exist in food allergy management. The questionnaire was developed and piloted at the Hamilton Health Sciences Corporation-McMaster University Medical Center Site. Using convenience sampling, participants were recruited from 6 allergy clinics in 5 Ontario cities. Patients of any age with food allergy who were evaluated by an allergist were considered for inclusion. Quantitative data was analyzed using descriptive statistics and frequency analysis. Audio recorded interviews with allergists were transcribed verbatim and analyzed using content analysis of grounded theory methodology.
Ninety-two food allergic families in the care of 6 allergists in Toronto, Hamilton, London, Kitchener, and Kingston participated in the study. Key areas requiring improvement in food allergy management were identified: 33% of families were not shown how to use an epinephrine auto-injector with a trainer, only 57% were asked to demonstrate an auto-injector, despite being on average at their 5th visit, and only about 30% felt very confident about when and how to give an auto-injector. Fifty percent of families did not receive sufficient information on medical identification and 21% did not receive information about support groups. Interviews with allergists revealed limitations in time and nursing resources.
Our study highlights the educational gaps and overall experiences of food allergic families in Ontario, and the challenges faced by the allergists managing them.
We published the Canadian 2003 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema (HAE; C1 inhibitor [C1-INH] deficiency) and updated this as Hereditary angioedema: a current state-of-the-art review: Canadian Hungarian 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema.
To update the International Consensus Algorithm for the Diagnosis, Therapy and Management of Hereditary Angioedema (circa 2010).
The Canadian Hereditary Angioedema Network (CHAEN)/Réseau Canadien d'angioédème héréditaire (RCAH) http://www.haecanada.com and cosponsors University of Calgary and the Canadian Society of Allergy and Clinical Immunology (with an unrestricted educational grant from CSL Behring) held our third Conference May 15th to 16th, 2010 in Toronto Canada to update our consensus approach. The Consensus document was reviewed at the meeting and then circulated for review.
This manuscript is the 2010 International Consensus Algorithm for the Diagnosis, Therapy and Management of Hereditary Angioedema that resulted from that conference.
Consensus approach is only an interim guide to a complex disorder such as HAE and should be replaced as soon as possible with large phase III and IV clinical trials, meta analyses, and using data base registry validation of approaches including quality of life and cost benefit analyses, followed by large head-to-head clinical trials and then evidence-based guidelines and standards for HAE disease management.